DuBois R N, Bishop P R, Graves-Deal R, Coffey R J
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Cell Growth Differ. 1995 May;6(5):523-9.
The epithelium lining the intestine undergoes rapid and continuous renewal. Growth factors play a role in intestinal epithelial growth regulation in vitro and in vivo. In this study, transforming growth factor alpha (TGF alpha) is shown to act as a mitogen and induce the expression of two zinc finger-containing immediate early genes [Zif268 (zinc finger protein 268) and Nup475 (nuclear protein 475)] in rat intestinal epithelial (RIE-1) cells in culture. These two gene products were initially isolated from serum-treated fibroblasts and represent growth-stimulated transcription factors. In TGF alpha-treated RIE-1 cells, nuclear run-on experiments demonstrate that TGF alpha induction of these two genes is regulated predominantly at the level of gene transcription. Utilizing in situ hybridization techniques, we show that systemic administration of TGF alpha induces expression of these two genes in the rat intestine. The predominant expression of zif268 is observed in the proliferative crypt compartment, whereas nup475 expression is concentrated in the postmitotic luminal compartment. These studies demonstrate that two immediate early genes, Nup475 and Zif268, are induced in intestinal epithelium in vitro and in vivo and thus may play a role in intestinal epithelial growth and/or differentiation.
肠道内的上皮组织会进行快速且持续的更新。生长因子在体外和体内的肠道上皮生长调节中发挥作用。在本研究中，转化生长因子α（TGFα）被证明可作为一种有丝分裂原，并在培养的大鼠肠道上皮（RIE-1）细胞中诱导两个含锌指的即刻早期基因[Zif268（锌指蛋白268）和Nup475（核蛋白475）]的表达。这两种基因产物最初是从血清处理的成纤维细胞中分离出来的，代表生长刺激转录因子。在TGFα处理的RIE-1细胞中，细胞核连续转录实验表明，TGFα对这两个基因的诱导主要在基因转录水平上受到调控。利用原位杂交技术，我们发现全身给予TGFα可诱导大鼠肠道中这两个基因的表达。在增殖的隐窝区观察到zif268的主要表达，而nup475的表达集中在有丝分裂后的管腔区。这些研究表明，两个即刻早期基因Nup475和Zif268在体外和体内的肠道上皮中均被诱导，因此可能在肠道上皮生长和/或分化中发挥作用。
